Safety, PK and Effectiveness of IV Peramivir in Elderly and Higher Risk Subjects With Uncomplicated Influenza

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Peramivir

About this trial

This is an interventional treatment trial for Influenza focused on measuring Acute uncomplicated, Elderly

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

A positive influenza Rapid Antigen Test (RAT) and/or a FDA-approved PCR test and at least one clinical sign or symptom consistent with acute influenza infection as listed below OR
Clinical signs and symptoms consistent with acute influenza infection consisting of an oral temperature ≥ 100°F (37.8°C) with at least one respiratory symptom of at least moderate severity (cough or rhinitis) and at least one constitutional symptom of at least moderate severity (myalgia [aches and pains], headache, feverishness, or fatigue)
Influenza symptom onset < 48 hours. However, due to historically delayed presentation for medical care in the adult population, approximately 20% of the elderly population may be enrolled with symptoms starting > 48-hours but ≤ 72-hours

Exclusion Criteria:

Women who plan to breast-feed for the first 48 hours after study drug administration
Subjects requiring hospital admission to treat medical condition(s) which could represent complications of influenza.
Recent worsening of any chronic medical condition consistent with complications of influenza
Current evidence of a bacterial infection requiring antibiotic treatment

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Peramivir

Arm Description

Single dose 600 mg IV injection

Outcomes

Primary Outcome Measures

Safety and Tolerability, as Measured by the Number of Adverse Events.

Safety was evaluated through assessment of Adverse Events (AEs).

Secondary Outcome Measures

Plasma Exposure of IV Peramivir as Measured by Drug Concentrations up to 3 Hours Post Infusion

Up to 3 plasma samples will be drawn, where possible: immediately following infusion, 30 mins to 1 hr post-infusion & 1 to 3 hrs post-infusion. Maximum concentration (Cmax), area under the concentration vs. time curve (AUC) from time 0 to 1 hour (AUC0-1), AUC from time 0 to 1.5 hours (AUC0-1.5), and AUC from time 0 to the last measurable time point (AUC0-last) were calculated in Phoenix® WinNonlin® v6.4. No summary statistics were reported due to the variation in the infusion time and sampling times.

Time to Resolution of Fever

Time for fever resolution based on subject diary record of temperature recorded twice daily. A subject had resolution of fever if he/she had an oral temperature < 37.4°C/99.4°F oral and no antipyretic medications were taken for at least 12 hours. The time to resolution of fever was estimated for each age group and overall using the Kaplan-Meier method with temperature and symptom relief medication information obtained from the Subject Diary data. Subjects who did not have resolution of fever were censored at the time of their last non-missing post-baseline temperature assessment.

Time to Resolution of Influenza Symptoms

Subjects were asked to provide an assessment of 7 influenza symptoms (cough, sore throat, nasal congestion, myalgia [aches and pains], headache, feverishness, and fatigue) on a 4-point severity scale (0, absent; 1, mild; 2, moderate; 3, severe) beginning at Screening then twice daily beginning on Day 1 through to Day 13, and prior to the subject's clinic visit on Day 14. Once all symptoms were scored a 0 or 1 for at least 48 hours, recordings were discontinued. The time to alleviation of symptoms, defined as the time from initiation of study drug until the start of the 21.5-hour period (24 hours less 10%), where all symptoms of influenza were recorded as none (0) or mild (1), was estimated overall and for each age group using the Kaplan-Meier method.

Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment.

Change in influenza viral titers was defined as the time-weighted change from Baseline in log_10 tissue culture infective dose_50 (TCID50/mL) and was summarized for each treatment group.

Time to Reduction in Viral Shedding

Assessment of viral shedding in bilateral, mid-nasal swab specimens taken at baseline and then on Day 3, 7 and 14.

Incidence of Influenza-related Complications

Study personnel evaluated the subject at Screening and Days 3, 7, and 14 for the presence of clinical signs and/or symptoms of the following influenza-related complications: Sinusitis, Otitis media, Bronchitis & Pneumonia. Note that subjects with clinical signs and/or symptoms consistent with bacterial infections, including otitis media, bronchitis, sinusitis, and/or pneumonia at Screening, were not eligible for enrollment in this study. If an influenza-related complication was suspected, then a targeted physical examination was to be conducted to confirm the presence or absence of the influenza-related complication.

Time to Return to Usual Activities

The ability to perform usual daily activities was assessed on a VAS (Visual Analogue Scale), where 0 indicates "unable to perform usual activities at all" and 10 indicates "able to perform usual activities.". The time to return to usual activities was the number of days from initiation of study drug until the subject recorded a rating of 10 (able to perform all usual activities fully) on the VAS; this was estimated for each age group and overall using the Kaplan-Meier method.

Full Information

NCT ID

NCT02635724

First Posted

December 17, 2015

Last Updated

February 26, 2021

Sponsor

BioCryst Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02635724

Brief Title

Safety, PK and Effectiveness of IV Peramivir in Elderly and Higher Risk Subjects With Uncomplicated Influenza

Official Title

A Phase 3, Multicenter, Single-arm, Open-label, Study to Evaluate the Safety, Pharmacokinetics and Effectiveness of Intravenous Peramivir in Elderly Subjects With Acute Uncomplicated Influenza Infection and in Subjects With Acute Uncomplicated Influenza Infection at Higher Risk for Influenza Complications

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

December 2015 (undefined)

Primary Completion Date

April 2018 (Actual)

Study Completion Date

September 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioCryst Pharmaceuticals

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

This study will evaluate the safety, pharmacokinetics and effectiveness of a single dose of 600 mg IV peramivir in the treatment of elderly subjects with acute uncomplicated influenza infection and in subjects with acute uncomplicated influenza infection at higher risk for influenza complications. All subjects will receive IV peramivir.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Influenza

Keywords

Acute uncomplicated, Elderly

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

74 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Peramivir

Arm Type

Experimental

Arm Description

Single dose 600 mg IV injection

Intervention Type

Drug

Intervention Name(s)

Peramivir

Other Intervention Name(s)

Rapivab

Primary Outcome Measure Information:

Title

Safety and Tolerability, as Measured by the Number of Adverse Events.

Description

Safety was evaluated through assessment of Adverse Events (AEs).

Time Frame

14 days

Secondary Outcome Measure Information:

Title

Plasma Exposure of IV Peramivir as Measured by Drug Concentrations up to 3 Hours Post Infusion

Description

Up to 3 plasma samples will be drawn, where possible: immediately following infusion, 30 mins to 1 hr post-infusion & 1 to 3 hrs post-infusion. Maximum concentration (Cmax), area under the concentration vs. time curve (AUC) from time 0 to 1 hour (AUC0-1), AUC from time 0 to 1.5 hours (AUC0-1.5), and AUC from time 0 to the last measurable time point (AUC0-last) were calculated in Phoenix® WinNonlin® v6.4. No summary statistics were reported due to the variation in the infusion time and sampling times.

Time Frame

up to 3 hours post peramivir infusion

Title

Time to Resolution of Fever

Description

Time for fever resolution based on subject diary record of temperature recorded twice daily. A subject had resolution of fever if he/she had an oral temperature < 37.4°C/99.4°F oral and no antipyretic medications were taken for at least 12 hours. The time to resolution of fever was estimated for each age group and overall using the Kaplan-Meier method with temperature and symptom relief medication information obtained from the Subject Diary data. Subjects who did not have resolution of fever were censored at the time of their last non-missing post-baseline temperature assessment.

Time Frame

14 days

Title

Time to Resolution of Influenza Symptoms

Description

Subjects were asked to provide an assessment of 7 influenza symptoms (cough, sore throat, nasal congestion, myalgia [aches and pains], headache, feverishness, and fatigue) on a 4-point severity scale (0, absent; 1, mild; 2, moderate; 3, severe) beginning at Screening then twice daily beginning on Day 1 through to Day 13, and prior to the subject's clinic visit on Day 14. Once all symptoms were scored a 0 or 1 for at least 48 hours, recordings were discontinued. The time to alleviation of symptoms, defined as the time from initiation of study drug until the start of the 21.5-hour period (24 hours less 10%), where all symptoms of influenza were recorded as none (0) or mild (1), was estimated overall and for each age group using the Kaplan-Meier method.

Time Frame

14 days

Title

Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment.

Description

Change in influenza viral titers was defined as the time-weighted change from Baseline in log_10 tissue culture infective dose_50 (TCID50/mL) and was summarized for each treatment group.

Time Frame

Change from baseline assessed on days 3, 7 and 14.

Title

Time to Reduction in Viral Shedding

Description

Assessment of viral shedding in bilateral, mid-nasal swab specimens taken at baseline and then on Day 3, 7 and 14.

Time Frame

14 days

Title

Incidence of Influenza-related Complications

Description

Study personnel evaluated the subject at Screening and Days 3, 7, and 14 for the presence of clinical signs and/or symptoms of the following influenza-related complications: Sinusitis, Otitis media, Bronchitis & Pneumonia. Note that subjects with clinical signs and/or symptoms consistent with bacterial infections, including otitis media, bronchitis, sinusitis, and/or pneumonia at Screening, were not eligible for enrollment in this study. If an influenza-related complication was suspected, then a targeted physical examination was to be conducted to confirm the presence or absence of the influenza-related complication.

Time Frame

14 days

Title

Time to Return to Usual Activities

Description

The ability to perform usual daily activities was assessed on a VAS (Visual Analogue Scale), where 0 indicates "unable to perform usual activities at all" and 10 indicates "able to perform usual activities.". The time to return to usual activities was the number of days from initiation of study drug until the subject recorded a rating of 10 (able to perform all usual activities fully) on the VAS; this was estimated for each age group and overall using the Kaplan-Meier method.

Time Frame

14 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: A positive influenza Rapid Antigen Test (RAT) and/or a FDA-approved PCR test and at least one clinical sign or symptom consistent with acute influenza infection as listed below OR Clinical signs and symptoms consistent with acute influenza infection consisting of an oral temperature ≥ 100°F (37.8°C) with at least one respiratory symptom of at least moderate severity (cough or rhinitis) and at least one constitutional symptom of at least moderate severity (myalgia [aches and pains], headache, feverishness, or fatigue) Influenza symptom onset < 48 hours. However, due to historically delayed presentation for medical care in the adult population, approximately 20% of the elderly population may be enrolled with symptoms starting > 48-hours but ≤ 72-hours Exclusion Criteria: Women who plan to breast-feed for the first 48 hours after study drug administration Subjects requiring hospital admission to treat medical condition(s) which could represent complications of influenza. Recent worsening of any chronic medical condition consistent with complications of influenza Current evidence of a bacterial infection requiring antibiotic treatment

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carol Clark, MD

Organizational Affiliation

Prof., Dept. of Emergency Medicine, Oakland University, William Beaumont School of Medicine, Royal Oak, MI

Official's Role

Principal Investigator

Facility Information:

Facility Name

Peramivir Investigational Site

City

Brooksville

State/Province

Florida

Country

United States

Facility Name

Peramivir Investigational Site

City

Lakeland

State/Province

Florida

Country

United States

Facility Name

Peramivir Investigational Site

City

Miami

State/Province

Florida

Country

United States

Facility Name

Peramivir Investigational Site

City

Saint Petersburg

State/Province

Florida

Country

United States

Facility Name

Peramivir Investigational Site

City

Tampa

State/Province

Florida

Country

United States

Facility Name

Peramivir investigative site

City

Indianapolis

State/Province

Indiana

Country

United States

Facility Name

Peramivir investigative site

City

Detroit

State/Province

Michigan

Country

United States

Facility Name

Peramivir Investigational Site

City

Dayton

State/Province

Ohio

Country

United States

Facility Name

Peramivir investigative site

City

Smithfield

State/Province

Pennsylvania

Country

United States

Facility Name

Peramivir Investigational Site

City

Houston

State/Province

Texas

Country

United States

Facility Name

Peramivir Investigative Site

City

San Antonio

State/Province

Texas

Country

United States

Facility Name

Peramivir investigative site

City

Splendora

State/Province

Texas

Country

United States

Facility Name

Peramivir Investigational Site

City

Draper

State/Province

Utah

Country

United States

Facility Name

Peramivir Investigational Site

City

Salt Lake City

State/Province

Utah

Country

United States

Facility Name

Peramivir investigative site

City

South Jordan

State/Province

Utah

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Influenza

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial